APPLICANT'S ABSTRACT: This application addresses two questions: 1. What is the psychological and neurobiological basis of drug craving, and 2. Why can drug craving persist so long after drug use (and withdrawal) has ended? These questions are posed in light of a new theory of drug addiction, The Incentive-Sensitization Theory (Robinson & Berridge, 1993). The theory posits that the repeated use of drugs such as cocaine or amphetamine sensitizes ventral striatal dopamine systems, rendering them perhaps permanently hypersensitive. The theory also posits that sensitized dopamine systems mediate a psychological process, the attribution of incentive salience, which transforms the perception of stimuli into subjective incentives that are attractive and "wanted". Sensitization of this dopamine system results in excessive incentive salience being attributed specifically (by associative learning) to drug-related stimuli. This leads in addiction to the subjective experience of excessive wanting or "craving". Further, the theory posits that these dopamine systems of drug craving are completely independent of systems that mediate both the subjective pleasurable effects of drugs and the subjective aversive effects of withdrawal. Thus, sensitization of these systems produces obsessive drug craving and compulsive drug-seeking behavior even if the drug is not expected to produce pleasure and even in the absence of subjective withdrawal symptoms. The incentive-sensitization theory of addiction makes specific testable predictions about the relation between "wanting" and "liking" drugs. Experiments are proposed here to test these predictions. For example, the theory predicts that repeated exposure to drugs will increase only the incentive effects of drug-related stimuli ("wanting") in the absence of an increase in hedonics ("liking"). A behavioral method will be developed to directly study the relation between "wanting" and "liking", and to determine if sensitization by cocaine or amphetamine can enhance instrumental behavioral measures of "wanting" without enhancing behavioral "affective reactivity" measures of "liking". These studies will provide a strong test of the incentive-sensitization theory. The truth of the theory is directly relevant to the clinical treatment of drug addiction because, if it is true, the theory makes novel predictions about the nature of medications that would effectively treat drug craving.